Active site mapping studies on transglutaminases using model substrates are underway. Special emphasis is being placed on the blood coagulation transglutaminases (plasma and platelet factor XIII). For these studies two series of peptide derivatives are being prepared and tested: (a) glutamine-containing peptides based on the amino acid sequence known to occur in the crosslinking regions of mammalian fibrins, and (b) lysine-containing peptides of structure designed to determine the influence of surrounding amino acid side chains. Selective limited cleavages of the transglutaminases are being carried out, together with end group analyses, preliminary to sequence analyses. Subunit structure, subunit dissociations, and reassociations are under investigation. The purpose of these studies is to relate the structure of the transglutaminases to their catalytic function and to determine the common structural features of these enzymes which have very similar catalytic functions and mechanisms.